Wound treatment with curcumin prevents hypertrophic scarring and promotes remodeling by inhibiting fibroblast activation and regulating collagen deposition.

More and more attention is paid to the prevention of hypertrophic scars (HS). This study aimed to investigate the mechanisms of topical curcumin application in alleviating HS secondary to wounds. Human dermal fibroblasts (HDFs) were cultured with transforming growth factor-β1 and varying concentrations of curcumin for 48 h. The proliferation activity, apoptosis and migration of HDFs were detected by CCK-8 assay, EdU assay, flow cytometry and wound healing assay, respectively. The expression of proteins implicated in fibroblast activation and collagen deposition was determined by Western blotting (WB). Curcumin (25 μmol/L, 28 days) was applied to rabbit ear wounds, and hypertrophic scarring was evaluated grossly and microscopically. We found that curcumin inhibited the proliferation and migration of HDFs and promoted cell apoptosis in a concentration-dependent manner. Curcumin at 10 and 25 μmol/L concentrations reduced the expression of Ki-67 and α-smooth muscle actin and increased cleaved caspase-3 expression and Bax/Bcl-2 ratio. Although the protein levels of collagen-I (COL-I), COL-III, matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were down-regulated, COL-III/COL-I and MMP-2/TIMP-1 ratios were maintained. Curcumin decreased the Manchester scar scale score, scar elevation index and collagen volume fraction of rabbit ear scars. Immunohistochemical results were generally consistent with the WB data. Unlike suppression of TIMP-1 in the entire region of the scar, curcumin reduced MMP-2 expression only in the edge part, which might be related to the alteration of cell polarity and orientation of fibroblasts. In conclusion, curcumin facilitates high-quality scars after wound healing by regulating fibroblast activation and collagen deposition.